Study of MK-3475 Alone or in Combination With Copanlisib in Relapsed or Refractory NK and T-cell Non-Hodgkin Lymphoma

NCT02535247 | Terminated Phase 1 Results DMC

• 1 other identifier: HM-075
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, single-arm, open label, study consisting of two cohorts. Cohort 2 explores the combination of copanlisib and pembrolizumab in patients with relapsed or refractory NKTCL, who have received at least 1 prior systemic therapy. Cohort 2 will include a phase 1 portion (cohort 2a) to determine the recommended phase 2 dose (RP2D) utilizing a standard 3+3 design, followed by a phase II portion where patients will be treated at the RP2D (cohort 2b). The primary endpoint for cohort 1 was progression-free survival; the primary endpoint for cohort 2a will be to determine RP2D for the combination therapy; and overall response rate at the end of 4 treatment cycles for cohort 2b. Patients will be assessed for response with PET CT or CT every 12 weeks using the revised Cheson criteria. Correlative endpoints will be exploratory and assess PD-1 expression on peripheral blood lymphocytes; peripheral blood T-cell and NK-cell functional assays; PD-1 and PD-L1 expression on tumor tissue; tumor infiltrating lymphocytes and gene expression panels using the nanostring technology as prognostic and predictive biomarkers, as well as monitoring of minimal residual disease via high-throughput sequencing of cell free tumor DNA, and exosome analysis.

Conditions

Lymphoma, T-Cell, Peripheral

Outcome Measures

Primary Outcomes (3)

• Progression Free Survival

  Based on RECIST v1.1

  3 Months

• Recommended Phase II Dose of the Combination of Pembrolizumab and Copanlisib

  6 months

• Determine Overall Response Rate by 4 Cycles of Combination of Pembrolizumab and Copanlisib

  6 months

Secondary Outcomes (3)

• Overall Survival

  6 Months

• Maximum Tolerated Dose of Pembrolizumab and Copanlisib

  6 months

• Expression of PD-1, PD-L1 and Tumor Infiltrating Lymphocytes (TIL) in Pre-treatment Tumor Specimens

  1 year

Other Outcomes (2)

• PD-1 Expression and Leukocyte Activation Markers on Circulating Lymphocytes Pre-treatment

  Week 3

• PD-1 Expression and Leukocyte Activation Markers on Circulating Lymphocytes Pre-treatment

  Week 6

Study Arms (2)

Treatment

EXPERIMENTAL

MK-3475 given intravenously at a fixed dose of 200mg every 3 weeks for up to 36 cycles

Drug: MK-3475

Combination

ACTIVE COMPARATOR

MK-3475 is given intravenously at a fixed dose of 200mg every 3 weeks Copanlisib is given intravenously at RP2D determined from Phase I study

Drug: MK-3475; Drug: Copanlisib

Interventions

MK-3475 DRUG

Also known as: Pembrolizumab

Combination; Treatment

Copanlisib DRUG

Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a histologically or cytologically confirmed relapsed/refractory mature T-cell lymphoma that has progressed after a minimum of 1 systemic therapy with any of the following T-cell histologies:
• Peripheral T-cell NHL, not other wise specified (PTCL, NOS)
• Anaplastic large cell T-cell lymphoma (ALCL)
• Anaplastic lymphoma kinase positive or negative
• Angioimmunoblastic T-cell lymphoma
• Subcutaneous panniculitis like T-cell lymphoma
• Follicular T-cell lymphoma
• Nodal peripheral T-cell lymphoma with TFH phenotype
• Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL)
• Enteropathy associated T-cell lymphoma
• Hepatosplenic T-cell lymphoma
• Extranodal NK/T-cell lymphoma, nasal type
• Unclassifiable PTCL
• Transformed cutaneous T-cell lymphoma (CTCL) to PTCL with systemic involvement (not local skin transformation).
• Be willing and able to sign written informed consent for the trial.

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 2 weeks of the first dose of treatment.
• Patients diagnosed with Adult T-cell Leukemia/Lymphoma (ATLL) or T-cell PLL
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., worse than Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with worse than Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has known active intraparenchymal lymphomatous central nervous system (CNS) lesions and/or lymphomatous meningitis. Subjects with previously treated CNS involvement by lymphoma may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain lesions, and are not using steroids for at least 7 days prior to trial treatment.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjoegren's syndrome will not be excluded from the study.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (1)

• Barta SK, Zain J, MacFarlane AW 4th, Smith SM, Ruan J, Fung HC, Tan CR, Yang Y, Alpaugh RK, Dulaimi E, Ross EA, Campbell KS, Khan N, Siddharta R, Fowler NH, Fisher RI, Oki Y. Phase II Study of the PD-1 Inhibitor Pembrolizumab for the Treatment of Relapsed or Refractory Mature T-cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2019 Jun;19(6):356-364.e3. doi: 10.1016/j.clml.2019.03.022. Epub 2019 Apr 3.

  PMID: 31029646 RESULT

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

Interventions

pembrolizumab; copanlisib

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Protocol Development Coordinator
• Organization: Fox Chase Cancer Center

ryan.romasko@fccc.edu

215-728-4097

Study Officials

• Henry Fung, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: MK-3475 is given intravenously at a fixed dose of 200mg every 3 weeks. Copanlisib is given intravenously at RP2D determined from Phase I study 18 in cohort 1 (pembrolizumab alone; completed); 27 in Cohort 2; 4-12 in cohort 2a (phase I); 18 in cohort 2b (phase II). Total up to 48

Study Record Dates

• First Submitted: August 26, 2015
• First Posted: August 28, 2015
• Study Start: January 5, 2016
• Primary Completion: February 25, 2020
• Study Completion: February 25, 2020
• Last Updated: July 8, 2022
• Results First Posted: July 8, 2022

Record last verified: 2022-06

Locations

US (1)